It has been known for many years that LCM virus can be altered by in vivo organ-virus interactions. For example, virus isolated from the liver of a persistently infected mouse may differ markedly in pathogenicity from virus isolated from the brain of the same animal. The objectives of the present proposal are centered around attempts to determine the factors responsible for the selection of these variants (or mutants), as well as the basis for their altered pathogenicity. Specifically, two virus types will be examined from mice persistently infected with the UBC strain of LCM. These viruses, easily distinguishable by plague morphology from parental input virus, behave quite differently when injected into mice. One causes rapid death of both neonatal and adult mice, while the other causes persitent infection in neonatal mice and either persistent infection or a slow wasting death in adult mice. Each virus (including the parental type) will be examined in the following ways: A) the efficiency of plating (EOP) will be determined at various temperatures to establish if any virus is a temperature sensitive (TS) mutant; B) the generation of defective interfering (DI) particles in neonatally-infected mice will be determined by use of an MDCK cell-killing assay; C) the induction of interferon in neonatal and adult mice will be examined by testing the pH stable component(s) in serum and spleen for ability to inhibit Vesicular Stomatitis virus plaque formation; D) peptide profiles will be examined by polyacrylamide gel electrophoresis (PAGE) using virus grown in the presence of radioactively labeled glucosamine and amino acids.